The chiral derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (LTPC) was used to form diastereomers of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) which were resolved on an achiral gas chromatographic column using a mass spectrometer as a detector. Rats were subcutaneously dosed with 40 mg/kg of (+/-) MDMA.HCl and blood was obtained by decapitation...
The behaviorally disruptive effects of the optical isomers of 1-(3,4-methylenedioxyphenyl-2-aminopropane) (MDA) and its N-methyl derivative (MDMA) were evaluated in 27 mice trained to bar-press for a liquid food reinforcement. In addition, a second study was conducted in which mice were pretreated with either saline or the 5-HT-2 antagonist, pirenpirone, prior to the administration of either...
Twenty-two rats were trained to discriminate either 1.5 mg/kg of 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a standard two-lever operant procedure. Once responding was stable, various doses of several serotonin (5-HT) antagonists, i.e., cyproheptadine (CYP), methysergide (UML), cinanserin (CIN), and methergoline (MCE), were administered in combination with 5-OMe DMT, to assess...
Stimulus generalization studies were conducted using rats trained to discriminate 1.0 mg/kg of the phenalkylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline in a two-lever operant procedure. The results suggest that certain indolealkylamine hallucinogens, including LSD and several alpha-methyltryptamine, N,N-dialkyltryptamine and beta-carboline derivatives,...
The discriminative effects of 5-methoxy-N,N-dimethyltryptamine (5-OMeDMT) were studied in rats trained to discriminate 1.5 mg/kg or 3.0 mg/kg 5-OMeDMT from saline. A series of antagonist and generalization tests revealed that (1) antagonism of the 5-OMeDMT stimulus response by the presumed serotonin antagonist BC-105 depended on the dose of 5-OMeDMT, (2) the 5-OMeDMT stimulus generalized to...
Rats were trained to discriminate injections of either 5-OMe DMT (1.5 mg/kg) or LSD (0.096 mg/kg) from saline in a two-lever drug discrimination task. After stable discrimination performances were attained (greater than 85%) in each group, dose-response generalizations between the two groups of animals were examined. The results revealed that the 5-OMe DMT-stimulus response generalized to LSD...
Twenty-four rats, trained to discriminate 1.0 mg/kg of (+/-)-DOM, i.e. (+/-)-2,5-dimethoxy-4-methylphenylisopropylamine, from saline under a VI-15 schedule of reinforcement, were challenged with a series of DOM homologs. The agents examined included the 4-ethyl (DOET), -propyl (DOPR), -butyl (DOBU), -tertiary butyl (DOTB) and -amyl (DOAM) derivatives as well as the R(-)- and S(+)-isomers of...
Rats trained to discriminate racemic 2,5-dimethoxy-4-methylphenylisopropylamine, (+/-)-DOM (1.0 mg/kg), from saline in a two-lever drug discrimination task were challenged with the optimal isomers of DOM as well as with several related agents which represent minor molecular modifications of the DOM structure. Generalization of the (+/-)-DOM stimulus was found to occur to R(-)-DOM, S(+)-DOM,...
Rats were trained to discriminate injections of 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT, 3.0 mg/kg) a hallucinogenic agent for which a serotonergic mechanism has been implicated, from saline in a two-lever drug discrimination task. After reliable levels of accuracy (greater than or equal to 85%) were attained, the ability of the 5-OMe DMT cue to generalize to 36 substituted...
Several 7-substituted derivatives of N,N-dimethyltryptamine (DMT) were prepared and evaluated in the rat fundus serotonin receptor assay and in a behavioral (discriminative stimulus) assay in rats. Both 7-Me- and 5-OMe-7-Me-DMT possess a higher pA2, and 5,7-(OMe)2-DMT a lower pA2, than that of DMT itself. Like DMT, all three of these compounds produce behavioral effects in rats which are...
Mono-O-demethylation of several 2,5-dimethoxyphenalkylamines increases their affinity for the serotonin receptors of the isolated rat fundus preparation. In several instances, demethylation of methoxyphenalkylamines results in compounds which produce an antagonism which is not of a competitive nature. With respect to 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), demethylation of the...
A choice between two levers in an operant chamber was used to train 24 rats, under a variable-interval 15 s schedule of sweetened milk reinforcement, to discriminate a hallucinogenic (psychotomimetic) agent, 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT), from saline administration. The 5-OMe DMT stimulus generalized in a dose-related manner to each of 14 tryptamine related analogs. With the...
The present investigation sought to determine whether the stimulus properties of morphine and lysergic acid diethylamide (LSD) would generalize to several narcotic analgesics which vary in their subjective effects. Morphine and saline served as discriminative stimuli for one group of rats in a 2-lever discrimination task. LSD and saline were discriminative stimuli for a second group. Depression...